Antibodies Evaluated in CSF vs. Blood

Many of the more recent case studies are using the antibody levels found in the cerebral spinal fluid (CSF) to diagnose and evaluate HE rather than the levels found in the blood. After all, the antibodies found in the CSF are the ones that may have crossed the blood brain barrier (BBB) and are the ones wreaking havoc on our brains.

In the case study, Steroid-responsive encephalopathy associated with autoimmune thyroiditis, the patient’s blood was checked for the antibody titers and the CSF was checked for other signs of disease. The CSF IgG index was normal in all tested. However, “The protein level was elevated in 17 patients (85%) (range, 55-680 mg/dL [0.055-0.68 g/dL]; referencerange, <45 mg/dL [<0.045 g/dL]).”

This case study also states, “The levels of thyroid antibodies were variable. All patients were encephalopathic, but antibody levels did not correspond to the severity of the clinical deficits. The presence of thyroid antibodies in serum, not the level, was the clinically relevant issue, indicating that SREAT should be considered in patients with encephalopathy even if thyroid antibody levels are only mildly elevated.”

The 2003 published case study, Antithyroid antibodies in the CSF: Their role in the pathogenesis of Hashimoto’s encephalopathy, compares the antibody levels found in the serum to those found in the CSF. The below table is copied from the study.

Table 2 Laboratory findings in patients with HE

Patient no. Q Alb. IgG index Serum TGAB CSF TGAB Serum TPOAB CSF TPOAB TGAB index TPOAB index Serum CIC CSF CIC 1 7.4 0.39 4,968 2,213 1,412 1,300 152.1 314.5 30 63 (n.v. < 9) (n.v. < 0.7) (n.v. < 50) (n.v. 0) (n.v. < 35) (n.v. 0) (n.v. < 1.3) (n.v. < 1.3) (n.v. < 35) (n.v. 0) 2 5.43 0.54 60 21 1,721 812 118.8 160.2 12 4 6.19 0.51 22 9 484 205 128.4 132.9 10 4 3 6.08 0.46 673 43 35 28 22.9 288.9 12 4 5.78 0.45 338 10 28 0 11.3 0 12 0 4 7.74 0.7 180 53 207 78 50.9 65.2 12 6 7.59 0.55 148 51 200 64 82 76.2 11 3 5 8.81 0.44 856 747 52 25 226.5 124.8 33 11 8.18 0.31 411 353 7 3 314.2 156.8 31 0 6 3.46 0.46 866 380 1,646 488 271.9 183.7 13 4 4.19 0.49 1,742 30 913 400 8.3 211.4 35 5 Indexes in Patients 2 to 6 were calculated before (top values) and after (bottom values) therapy or spontaneous clinical improvement. The titres of TGAB and TPOAB are measured in IU/mL. The titres of CIC are measured in mEq/L. HE = Hashimoto encephalopathy; Q Alb. = albumin CSF/serum quotient; IgG = immunoglobulin G; TGAB = antithyroglobulin antibodies; TPOAB = antithyroid peroxidase antibodies; CIC = circulating immune complexes; n.v. = normal value.

When you examine the serum TPOAb and the CSF TPOAb level changes from the 5 patients with before/after data (I colored in blue) all patients except Patient 6 experienced a greater percentage decrease in the CSF antibody levels compared to the serum antibody levels.

Ignoring Patient 1 (who was lost to follow-up), all patients except patient 3 were treated with steroids. Patient 3 experienced a spontaneous recovery. Although her TPO antibodies in her blood did not decrease much, the TPO antibodies in her CSF decreased to 0 after her recovery. Patient 2 experienced dramatic recovery and a significant decrease in the antibodies. On the contrary, Patient 6 had clinical recovery in spite of his CSF TPO antibodies only slightly decreasing and still remaining high above normal. Patients 4 and 5 did experience decrease in TPO antibodies however did not experience clinical recovery. In reading their symptoms and history, it is possible Patients 4 and 5 have the more progressive type of HE (as opposed to the stroke-like relapsing type) which has been noted as having more difficulty responding to steroids and treatments.

Based on this data, there is no apparent correlation between the levels of the TPO autoantibodies in the blood or CSF with the symptoms of HE.

When you examine the serum TGAb and the CSF TGAb level changes from the 5 patients with before/after data (I colored in green) the data much better supports the possibility of a correlation of antibody level to symptoms. All patients that experienced a recovery experienced a significant decrease in the CSF of the TGAb. Patient 4 was the only patient who did not experience a significant decrease in the TGAb level, and this patient did not experience clinical improvement. Although Patient 5 experienced more than 50% decrease of the TGAb, the CSF level still remained very high (more than 7 times the levels of the other patients). Patient 5 did not experience clinical recovery, possibly because the TGAb remained so high.

The levels of the TGAB in the CSF better support correlation to symptoms compared to the levels in the blood. Just look at patient 6 who experienced recovery with TGAb levels drastically decreasing in the CSF, but actually increasing in the serum.

Another case study supports the correlation of TGAb levels with clinical symptoms and recovery, An 85-year-old Case with Hashimoto’s Encephalopathy, Showing Spontaneous Complete Remission. Note: The autoantibody against the amino (NH₂) terminal region of α-enolase was positive in the serum of this patient. “Thyroidperoxidase antibody was within normal limits (1.8 IU/ml, normal value less than 10.0 IU/ml), but anti-thyroglobulin antibody (TGAb) was markedly elevated (29,043 IU/ml, normal value less than 10.0 IU/ml).”

The patient’s symptoms improved without steroid treatment. He was continuing to receive thyroxine treatment for a previous thyroid problem. ” TSH showed no obvious alterations and TGAb in serum increased after admission, while TGAb in CSF clearly decreased in conjunction with the disappearance of neuropsychological symptoms.”

The article also confirmed the benefits of testing the CSF for the antibodies because although anti-thyroid antibodies commonly appear in the serum of healthy individuals, “anti-thyroid autoantibodies in CSF, including TGAb, are considered to play an important role in manifesting CNS symptoms because these antibodies are undetectable in patients with autoimmune thyroiditis or other neurological disorders.”

According to the study, Long-term Treatment of Hashimoto’s Encephalopathy, 100% of HE patients studied had elevated anti-TPO antibodies in their serum and 73% had elevated anti-TG antibodies in their serum. There was no mention of the CSF levels.

This study also noted the possibility of intrathecal synthesis of the antibodies.

My ending thoughts on this post:

Elevated antithyroid antibodies has been one important factor in diagnosing HE.  Elevated anti-TPO antibodies (TPOAb) being the most common among HE patients, with elevated antithyroglobulin antibodies (TGAb) also being a very common marker for diagnosing HE.

In the case studies prior to 2005 it appears the antibody levels were examined primarily in the serum.  More recent studies have indicated it may be more useful to examine the antibody levels in the CSF.

Recent case studies have shown a possible correlation with the level of TGAb in the CSF and the acuteness of the HE symptoms.  If this correlation proves to be true, it would be a very good indicator of when treatment has been successful and when tapering off steroids or changing other treatments would be safer.

If a patient is presenting with acute symptoms of HE, the CSF should be examined before and after treatment for levels of antithyroid antibodies, specifically TGAb.